Symptom Profile of Post–COVID-19 Syndrome Across Variants, Vaccination Status

In patients with 12 or more weeks of persistent symptoms following SARS-CoV-2 infection, distinct self-reported symptom evolutions, or clusters were identified.

Distinct self-reported symptom evolutions, or clusters, have been identified in individuals who experience more than 12 weeks of persistent symptoms following a SARS-CoV-2 infection — potentially due to differing pathophysiology. These are the findings of a study uploaded to medRvix, the preprint server.

Self-reported symptoms of COVID-19 helped increase the understanding of SARS-CoV-2 during the pandemic. Further, it has made it possible to track the long-term effects of COVID-19 outside a hospital setting. Now, researchers of the current study want to characterize how post-COVID syndrome manifests with different patterns to help individualize therapy for affected survivors.

According to this team of researchers, there are no available studies that compare symptom pattern of post-COVID syndrome among COVID-19 vaccination status and infection with various variants. Further, they state there are no studies that have characterized post-COVID syndrome through the modeling of longitudinally collected samples.

For this study, researchers conducted a prospective, longitudinal cohort study that analyzed data derived from regular health reports through the COVID Symptom Study (CSS) smartphone application in a UK population of patients. They sought to identify symptom profiles for post-COVID syndrome across the dominant variants in 2020 and 2021, as well as across vaccination status at the time of infection, with use of a large sample containing self-reports of symptoms. They hypothesized that among the heterogeneous presentation of post- COVID syndrome, distinct symptom profiles and phenotypes could be identified that might be associated with varying pathophysiology.

The main result from this analysis demonstrated that the [post-COVID syndrome] clusters differed in their relation to individuals’ daily activities.

The researchers identified distinct profiles of symptoms for post-COVID syndrome within and across the different variants: 4 endotypes were identified for infections due to the wild-type variant; 7 endotypes were identified for the Alpha variant, and 5 endotypes were identified for the Delta variant.

Data from a total of 336,652 participants were analyzed via health reports from the CSS app. These individuals had reported feeling physically normal for 30 days or more prior to testing positive for SARS-CoV-2 infection. Overall, 9323 of these patients subsequently developed long-COVID, which was defined as “symptoms lasting longer than 28 days.” Of these individuals, 1459 had post-COVID syndrome, which was defined as “more than 12 weeks of symptoms.”

The symptom profile per variant and per population (vaccinated vs unvaccinated) in individuals with post- COVID syndrome was evaluated. In those with the wild-type variant, only 20 symptoms were considered; in contrast, for both the Alpha and the Delta variants, all 34 available symptoms were considered.

Across all variants, 3 main symptom profiles were identified:

  1. A central neurologic cluster of symptoms, frequently without a major impact of other symptoms (alpha and delta variants);
  2. A cardiorespiratory cluster of symptoms, typically linked to such symptoms as severe dyspnea; and
  3. A systemic/inflammatory cluster that included the most severe, debilitating multi-organ symptoms and often manifesting other immune-related symptoms.

Further, gastrointestinal symptoms were often predominantly isolated within a single (ie, smallest) cluster, which was evident across the 3 variants. Additionally, immune-related and cutaneous symptoms manifested largely within a single cluster, with some minor occurrences of the symptoms within other clusters.

Limitations of the current study included the fact that CSS app users are not fully representative of the UK populations (ie, more middle-aged individuals, more likely to be female, more likely to be of a higher educational status, and overrepresentative of health care workers). Further, different cultural and economic experiences may affect the presentation of COVID-19 and the reporting of symptoms.

“The main result from this analysis demonstrated that the [post-COVID syndrome] clusters differed in their relation to individuals’ daily activities,” the researchers noted.

They also stated that “further investigation into mechanisms underlying [post-COVID syndrome] should consider subdividing affected individuals into different subgroups, which may increase the ability to identify distinct processes underlying these symptom clusters.”

Disclosure: Some of the study authors have declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures. 


Canas LS, Molteni E, Deng J, et al. Profiling post-COVID syndrome across different variants of SARS-CoV-2. medRxiv. Published online July 31, 2022. doi:10.1101/2022.07.28.22278159